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| | ==Crystal structure of CEACAM3== | | ==Crystal structure of CEACAM3== |
| - | <StructureSection load='6aw1' size='340' side='right' caption='[[6aw1]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='6aw1' size='340' side='right'caption='[[6aw1]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6aw1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AW1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AW1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6aw1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AW1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CEACAM3, CD66D, CGM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6aw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aw1 OCA], [http://pdbe.org/6aw1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aw1 RCSB], [http://www.ebi.ac.uk/pdbsum/6aw1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aw1 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6aw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aw1 OCA], [https://pdbe.org/6aw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aw1 RCSB], [https://www.ebi.ac.uk/pdbsum/6aw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aw1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CEAM3_HUMAN CEAM3_HUMAN]] Major granulocyte receptor mediating recognition and efficient opsonin-independent phagocytosis of CEACAM-binding microorganisms, including Neissiria, Moxarella and Haemophilus species, thus playing an important role in the clearance of pathogens by the innate immune system. Responsible for RAC1 stimulation in the course of pathogen phagocytosis.<ref>PMID:12864848</ref> <ref>PMID:14707113</ref> | + | [https://www.uniprot.org/uniprot/CEAM3_HUMAN CEAM3_HUMAN] Major granulocyte receptor mediating recognition and efficient opsonin-independent phagocytosis of CEACAM-binding microorganisms, including Neissiria, Moxarella and Haemophilus species, thus playing an important role in the clearance of pathogens by the innate immune system. Responsible for RAC1 stimulation in the course of pathogen phagocytosis.<ref>PMID:12864848</ref> <ref>PMID:14707113</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bonsor, D A]] | + | [[Category: Large Structures]] |
| - | [[Category: Sundberg, E J]] | + | [[Category: Bonsor DA]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Sundberg EJ]] |
| Structural highlights
Function
CEAM3_HUMAN Major granulocyte receptor mediating recognition and efficient opsonin-independent phagocytosis of CEACAM-binding microorganisms, including Neissiria, Moxarella and Haemophilus species, thus playing an important role in the clearance of pathogens by the innate immune system. Responsible for RAC1 stimulation in the course of pathogen phagocytosis.[1] [2]
Publication Abstract from PubMed
Helicobacter pylori infects half of the world's population, and strains that encode the cag type IV secretion system for injection of the oncoprotein CagA into host gastric epithelial cells are associated with elevated levels of cancer. CagA translocation into host cells is dependent on interactions between the H. pylori adhesin protein HopQ and human CEACAMs. Here, we present high-resolution structures of several HopQ-CEACAM complexes and CEACAMs in their monomeric and dimeric forms establishing that HopQ uses a coupled folding and binding mechanism to engage the canonical CEACAM dimerization interface for CEACAM recognition. By combining mutagenesis with biophysical and functional analyses, we show that the modes of CEACAM recognition by HopQ and CEACAMs themselves are starkly different. Our data describe precise molecular mechanisms by which microbes exploit host CEACAMs for infection and enable future development of novel oncoprotein translocation inhibitors and H. pylori-specific antimicrobial agents.
The Helicobacter pylori adhesin protein HopQ exploits the dimer interface of human CEACAMs to facilitate translocation of the oncoprotein CagA.,Bonsor DA, Zhao Q, Schmidinger B, Weiss E, Wang J, Deredge D, Beadenkopf R, Dow B, Fischer W, Beckett D, Wintrode PL, Haas R, Sundberg EJ EMBO J. 2018 May 3. pii: embj.201798664. doi: 10.15252/embj.201798664. PMID:29724755[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McCaw SE, Schneider J, Liao EH, Zimmermann W, Gray-Owen SD. Immunoreceptor tyrosine-based activation motif phosphorylation during engulfment of Neisseria gonorrhoeae by the neutrophil-restricted CEACAM3 (CD66d) receptor. Mol Microbiol. 2003 Aug;49(3):623-37. PMID:12864848
- ↑ Schmitter T, Agerer F, Peterson L, Munzner P, Hauck CR. Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific pathogens. J Exp Med. 2004 Jan 5;199(1):35-46. doi: 10.1084/jem.20030204. PMID:14707113 doi:http://dx.doi.org/10.1084/jem.20030204
- ↑ Bonsor DA, Zhao Q, Schmidinger B, Weiss E, Wang J, Deredge D, Beadenkopf R, Dow B, Fischer W, Beckett D, Wintrode PL, Haas R, Sundberg EJ. The Helicobacter pylori adhesin protein HopQ exploits the dimer interface of human CEACAMs to facilitate translocation of the oncoprotein CagA. EMBO J. 2018 May 3. pii: embj.201798664. doi: 10.15252/embj.201798664. PMID:29724755 doi:http://dx.doi.org/10.15252/embj.201798664
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